Sensitivity of Pliocene Arctic climate to orbital forcing, atmospheric CO2 and sea ice albedo parameterisation

General circulation model (GCM) simulations of the mid-Pliocene Warm Period (mPWP, 3.264 to 3.025Myr ago) do not reproduce the magnitude of Northern Hemisphere high latitude surface air and sea surface temperature (SAT and SST) warming that proxy data indicate. There is also large uncertainty regarding the state of sea ice cover in the mPWP. Evidence for both perennial and seasonal mPWP Arctic sea ice is found through analyses of marine sediments, whilst in a multi-model ensemble of mPWP climate simulations, half of the ensemble simulated ice-free summer Arctic conditions. Given the strong influence that sea ice exerts on high latitude temperatures, an understanding of the nature of mPWP Arctic sea ice would be highly beneficial. Using the HadCM3 GCM, this paper explores the impact of various combinations of potential mPWP orbital forcing, atmospheric CO2concentrations and minimum sea ice albedo on sea ice extent and high latitude warming. The focus is on the Northern Hemisphere, due to availability of proxy data, and the large data–model discrepancies in this region. Changes in orbital forcings are demonstrated to be sufficient to alter the Arctic sea ice simulated by HadCM3 from perennial to seasonal. However, this occurs only when atmospheric CO2concentrations exceed 300 ppm. Reduction of the minimum sea ice albedo from 0.5 to 0.2 is also sufficient to simulate seasonal sea ice, with any of the combinations of atmospheric CO2and orbital forcing. Compared to a mPWP control simulation, monthly mean increases north of 60◦N of up to 4.2◦C (SST) and 9.8◦C (SAT) are simulated. With varying CO2, orbit and sea ice albedo values we are able to reproduce proxy temperature records that lean towards modest levels of high latitude warming, but other proxy data showing greater warming remain beyond the reach of our model. This highlights the importance of additional proxy records at high latitudes and ongoing efforts to compare proxy signals between sites

The PRISM4 (mid-Piacenzian) paleoenvironmental reconstruction

The mid-Piacenzian is known as a period of relative warmth when compared to the present day. A comprehensive understanding of conditions during the Piacenzian serves as both a conceptual model and a source for boundary conditions and means of verification of global climate model experiments. In this paper we present the PRISM4 reconstruction, a palaeoenvironmental reconstruction of the mid-Piacenzian (~3 Ma) containing data for palaeogeography, land and sea-ice, sea-surface temperature, vegetation, soils and lakes. Our retrodicted palaeogeography takes into account glacial isostatic adjustments and changes in dynamic topography. Soils and lakes, both significant as land surface features, are introduced to the PRISM reconstruction for the first time. Sea-surface temperature and vegetation reconstructions are unchanged but now have confidence assessments. The PRISM4 reconstruction is being used as boundary condition data for the Pliocene Model Intercomparison Project, Phase 2 (PlioMIP2) experiments

Macroevolutionary consequences of profound climate change on niche evolution in marine molluscs over the past three million years

In order to predict the fate of biodiversity in a rapidly changing world, we must first understand how species adapt to new environmental conditions. The long-term evolutionary dynamics of species’ physiological tolerances to differing climatic regimes remain obscure. Here, we unite palaeontological and neontological data to analyse whether species’ environmental tolerances remain stable across 3 Myr of profound climatic changes using 10 phylogenetically, ecologically and developmentally diverse mollusc species from the Atlantic and Gulf Coastal Plains, USA. We additionally investigate whether these species’ upper and lower thermal tolerances are constrained across this interval. We find that these species’ environmental preferences are stable across the duration of their lifetimes, even when faced with significant environmental perturbations. The results suggest that species will respond to current and futurewarming either by altering distributions to track suitable habitat or, if the pace of change is too rapid, by going extinct. Our findings also support methods that project species’ present-day environmental requirements to future climatic landscapes to assess conservation risks

Targeting tumour re-wiring by triple blockade of mTORC1, epidermal growth factor, and oestrogen receptor signalling pathways in endocrine-resistant breast cancer

Background Endocrine therapies are the mainstay of treatment for oestrogen receptor (ER)-positive (ER+) breast cancer (BC). However, resistance remains problematic largely due to enhanced cross-talk between ER and growth factor pathways, circumventing the need for steroid hormones. Previously, we reported the anti-proliferative effect of everolimus (RAD001-mTORC1 inhibitor) with endocrine therapy in resistance models; however, potential routes of escape from treatment via ERBB2/3 signalling were observed. We hypothesised that combined targeting of three cellular nodes (ER, ERBB, and mTORC1) may provide enhanced long-term clinical utility. Methods A panel of ER+ BC cell lines adapted to long-term oestrogen deprivation (LTED) and expressing ESR1wt or ESR1Y537S, modelling acquired resistance to an aromatase-inhibitor (AI), were treated in vitro with a combination of RAD001 and neratinib (pan-ERBB inhibitor) in the presence or absence of oestradiol (E2), tamoxifen (4-OHT), or fulvestrant (ICI182780). End points included proliferation, cell signalling, cell cycle, and effect on ER-mediated transactivation. An in-vivo model of AI resistance was treated with monotherapies and combinations to assess the efficacy in delaying tumour progression. RNA-seq analysis was performed to identify changes in global gene expression as a result of the indicated therapies. Results Here, we show RAD001 and neratinib (pan-ERBB inhibitor) caused a concentration-dependent decrease in proliferation, irrespective of the ESR1 mutation status. The combination of either agent with endocrine therapy further reduced proliferation but the maximum effect was observed with a triple combination of RAD001, neratinib, and endocrine therapy. In the absence of oestrogen, RAD001 caused a reduction in ER-mediated transcription in the majority of the cell lines, which associated with a decrease in recruitment of ER to an oestrogen-response element on the TFF1 promoter. Contrastingly, neratinib increased both ER-mediated transactivation and ER recruitment, an effect reduced by the addition of RAD001. In-vivo analysis of an LTED model showed the triple combination of RAD001, neratinib, and fulvestrant was most effective at reducing tumour volume. Gene set enrichment analysis revealed that the addition of neratinib negated the epidermal growth factor (EGF)/EGF receptor feedback loops associated with RAD001. Conclusions Our data support the combination of therapies targeting ERBB2/3 and mTORC1 signalling, together with fulvestrant, in patients who relapse on endocrine therapy and retain a functional ER

Pathologic and biologic response to preoperative endocrine therapy in patients with ER-positive ductal carcinoma in situ

Abstract Background Endocrine therapy is commonly recommended in the adjuvant setting for patients as treatment for ductal carcinoma in situ (DCIS). However, it is unknown whether a neoadjuvant (preoperative) anti-estrogen approach to DCIS results in any biological change. This study was undertaken to investigate the pathologic and biomarker changes in DCIS following neoadjuvant endocrine therapy compared to a group of patients who did not undergo preoperative anti-estrogenic treatment to determine whether such treatment results in detectable histologic alterations. Methods Patients (n = 23) diagnosed with ER-positive pure DCIS by stereotactic core biopsy were enrolled in a trial of neoadjuvant anti-estrogen therapy followed by definitive excision. Patients on hormone replacement therapy, with palpable masses, or with histologic or clinical suspicion of invasion were excluded. Premenopausal women were treated with tamoxifen and postmenopausal women were treated with letrozole. Pathologic markers of proliferation, inflammation, and apoptosis were evaluated at baseline and at three months. Biomarker changes were compared to a cohort of patients who had not received preoperative treatment. Results Median age of the cohort was 53 years (range 38–78); 14 were premenopausal. Following treatment, predominant morphologic changes included increased multinucleated histiocytes and degenerated cells, decreased duct extension, and prominent periductal fibrosis. Two postmenopausal patients had ADH only with no residual DCIS at excision. Postmenopausal women on letrozole had significant reduction of PR, and Ki67 as well as increase in CD68-positive cells. For premenopausal women on tamoxifen treatment, the only significant change was increase in CD68. No change in cleaved caspase 3 was found. Two patients had invasive cancer at surgery. Conclusion Preoperative therapy for DCIS is associated with significant pathologic alterations. These changes may be clinically significant. Further work is needed to identify which women may be the best candidates for such treatment for DCIS, and whether best responders may safely avoid surgical intervention. Trial Registration ClinicalTrials.gov NCT0029074

Paleoclimate Implications for Human-Made Climate Change

Paleoclimate data help us assess climate sensitivity and potential human-made climate effects. We conclude that Earth in the warmest interglacial periods of the past million years was less than 1{\deg}C warmer than in the Holocene. Polar warmth in these interglacials and in the Pliocene does not imply that a substantial cushion remains between today's climate and dangerous warming, but rather that Earth is poised to experience strong amplifying polar feedbacks in response to moderate global warming. Thus goals to limit human-made warming to 2{\deg}C are not sufficient - they are prescriptions for disaster. Ice sheet disintegration is nonlinear, spurred by amplifying feedbacks. We suggest that ice sheet mass loss, if warming continues unabated, will be characterized better by a doubling time for mass loss rate than by a linear trend. Satellite gravity data, though too brief to be conclusive, are consistent with a doubling time of 10 years or less, implying the possibility of multi-meter sea level rise this century. Observed accelerating ice sheet mass loss supports our conclusion that Earth's temperature now exceeds the mean Holocene value. Rapid reduction of fossil fuel emissions is required for humanity to succeed in preserving a planet resembling the one on which civilization developed.Comment: 32 pages, 9 figures; final version accepted for publication in "Climate Change at the Eve of the Second Decade of the Century: Inferences from Paleoclimate and Regional Aspects: Proceedings of Milutin Milankovitch 130th Anniversary Symposium" (eds. Berger, Mesinger and Sijaci

Sea Surface Temperature of the mid-Piacenzian Ocean:A Data-Model Comparison

The mid-Piacenzian climate represents the most geologically recent interval of long-term average warmth relative to the last million years, and shares similarities with the climate projected for the end of the 21st century. As such, it represents a natural experiment from which we can gain insight into potential climate change impacts, enabling more informed policy decisions for mitigation and adaptation. Here, we present the first systematic comparison of Pliocene sea surface temperature (SST) between an ensemble of eight climate model simulations produced as part of PlioMIP (Pliocene Model Intercomparison Project) with the PRISM (Pliocene Research, Interpretation and Synoptic Mapping) Project mean annual SST field. Our results highlight key regional and dynamic situations where there is discord between the palaeoenvironmental reconstruction and the climate model simulations. These differences have led to improved strategies for both experimental design and temporal refinement of the palaeoenvironmental reconstruction

Evaluation of Arctic warming in mid-Pliocene climate simulations

Palaeoclimate simulations improve our understanding of the climate, inform us about the performance of climate models in a different climate scenario, and help to identify robust features of the climate system. Here, we analyse Arctic warming in an ensemble of 16 simulations of the mid-Pliocene Warm Period (mPWP), derived from the Pliocene Model Intercomparison Project Phase 2 (PlioMIP2). The PlioMIP2 ensemble simulates Arctic (60–90∘ N) annual mean surface air temperature (SAT) increases of 3.7 to 11.6 ∘C compared to the pre-industrial period, with a multi-model mean (MMM) increase of 7.2 ∘C. The Arctic warming amplification ratio relative to global SAT anomalies in the ensemble ranges from 1.8 to 3.1 (MMM is 2.3). Sea ice extent anomalies range from −3.0 to −10.4×10^{6} km^{2}, with a MMM anomaly of −5.6×10^{6} km^{2}, which constitutes a decrease of 53 % compared to the pre-industrial period. The majority (11 out of 16) of models simulate summer sea-ice-free conditions (≤1×10^{6} km^{2}) in their mPWP simulation. The ensemble tends to underestimate SAT in the Arctic when compared to available reconstructions, although the degree of underestimation varies strongly between the simulations. The simulations with the highest Arctic SAT anomalies tend to match the proxy dataset in its current form better. The ensemble shows some agreement with reconstructions of sea ice, particularly with regard to seasonal sea ice. Large uncertainties limit the confidence that can be placed in the findings and the compatibility of the different proxy datasets. We show that while reducing uncertainties in the reconstructions could decrease the SAT data–model discord substantially, further improvements are likely to be found in enhanced boundary conditions or model physics. Lastly, we compare the Arctic warming in the mPWP to projections of future Arctic warming and find that the PlioMIP2 ensemble simulates greater Arctic amplification than CMIP5 future climate simulations and an increase instead of a decrease in Atlantic Meridional Overturning Circulation (AMOC) strength compared to pre-industrial period. The results highlight the importance of slow feedbacks in equilibrium climate simulations, and that caution must be taken when using simulations of the mPWP as an analogue for future climate change

A return to large-scale features of Pliocene climate: the Pliocene Model Intercomparison Project Phase 2

The Pliocene epoch has great potential to improve our understanding of the long-term climatic and environmental consequences of an atmospheric CO2 concentration near ~ 400 parts per million by volume. Here we present the large-scale features of Pliocene climate as simulated by a new ensemble of climate models of varying complexity and spatial resolution and based on new reconstructions of boundary conditions (the Pliocene Model Intercomparison Project Phase 2; PlioMIP2). As a global annual average, modelled surface air temperatures increase by between 1.4 and 4.7 °C relative to pre-industrial with a multi-model mean value of 2.8 °C. Annual mean total precipitation rates increase by 6 % (range: 2 %–13 %). On average, surface air temperature (SAT) increases are 1.3 °C greater over the land than over the oceans, and there is a clear pattern of polar amplification with warming polewards of 60° N and 60° S exceeding the global mean warming by a factor of 2.4. In the Atlantic and Pacific Oceans, meridional temperature gradients are reduced, while tropical zonal gradients remain largely unchanged. Although there are some modelling constraints, there is a statistically significant relationship between a model's climate response associated with a doubling in CO2 (Equilibrium Climate Sensitivity; ECS) and its simulated Pliocene surface temperature response. The mean ensemble earth system response to doubling of CO2 (including ice sheet feedbacks) is approximately 50 % greater than ECS, consistent with results from the PlioMIP1 ensemble. Proxy-derived estimates of Pliocene sea-surface temperatures are used to assess model estimates of ECS and indicate a range in ECS from 2.5 to 4.3 °C. This result is in general accord with the range in ECS presented by previous IPCC Assessment Reports

The Pliocene Model Intercomparison Project Phase 2: large-scale climate features and climate sensitivity

The Pliocene epoch has great potential to improve our understanding of the long-term climatic and environmental consequences of an atmospheric CO2 concentration near ∼400 parts per million by volume. Here we present the large-scale features of Pliocene climate as simulated by a new ensemble of climate models of varying complexity and spatial resolution based on new reconstructions of boundary conditions (the Pliocene Model Intercomparison Project Phase 2; PlioMIP2). As a global annual average, modelled surface air temperatures increase by between 1.7 and 5.2 ∘C relative to the pre-industrial era with a multi-model mean value of 3.2 ∘C. Annual mean total precipitation rates increase by 7 % (range: 2 %–13 %). On average, surface air temperature (SAT) increases by 4.3 ∘C over land and 2.8 ∘C over the oceans. There is a clear pattern of polar amplification with warming polewards of 60∘ N and 60∘ S exceeding the global mean warming by a factor of 2.3. In the Atlantic and Pacific oceans, meridional temperature gradients are reduced, while tropical zonal gradients remain largely unchanged. There is a statistically significant relationship between a model's climate response associated with a doubling in CO2 (equilibrium climate sensitivity; ECS) and its simulated Pliocene surface temperature response. The mean ensemble Earth system response to a doubling of CO2 (including ice sheet feedbacks) is 67 % greater than ECS; this is larger than the increase of 47 % obtained from the PlioMIP1 ensemble. Proxy-derived estimates of Pliocene sea surface temperatures are used to assess model estimates of ECS and give an ECS range of 2.6–4.8 ∘C. This result is in general accord with the ECS range presented by previous Intergovernmental Panel on Climate Change (IPCC) Assessment Reports